10-Year efficacy and co-morbidity outcomes of a phase III randomised trial of conventional vs. hypofractionated high dose intensity modulated radiotherapy for prostate cancer (CHHiP; CRUK/06/016).
Authors: Isabel Syndikus, Clare Griffin, Lara Philipps, Alison Tree, Vincent Khoo, Alison Jane Birtle, Ananya Choudhury, Catherine Ferguson, Joe M. O'Sullivan, Miguel Panades, Yvonne L. Rimmer, Christopher D. Scrase, John Staffurth, Clare Cruickshank, Shama Hassan, Julia Pugh, David P. Dearnaley, Emma Hall
Journal: Journal of Clinical Oncology (2023)

304 Background: Five-year results from the CHHiP trial indicated that moderate hypofractionation of 60 Gray (Gy)/20 fractions (f) was non-inferior to 74Gy/37f (Lancet Oncology, 2016). Reporting of long-term efficacy and side effects is essential in a patient population that remain at risk of recurrence years after treatment. Here we report specific co-morbidity data collected at 10 years and an update of efficacy. Methods: Between October 2002 and June 2011, 3216 men with node negative T1b-T3a localised prostate cancer with risk of seminal vesical involvement ≤30% were randomised (1:1:1 ratio) to 74Gy/37f (control), 60Gy/20f or 57Gy/19f. Patients received 3-6 months of androgen deprivation prior to radiotherapy. The primary endpoint was time to biochemical failure (Phoenix consensus guidelines) or clinical failure (BCF). The non-inferiority design specified a critical hazard ratio (HR) of 1.208 for each hypofractionated schedule compared to control. Data on specific radiotherapy related co-morbidities were collected at 10-year follow-up and are presented as frequency and percentages. Analysis was by intention-to-treat; HRs quoted are unadjusted. Results: With a median follow up of 12.1 years, 10-year BCF-free rates (95% CI) were 74Gy: 76.0% (73.1%, 78.6%); 60Gy: 79.8% (77.1%, 82.3%) and 57Gy: 73.4% (70.5%, 76.1%). For 60Gy/20f, non-inferiority was confirmed: HR 60 =0.84 (90% CI 0.72, 0.97) with borderline significance for superiority (HR=0.84 (95% CI 0.70, 1.00). As in the primary analysis, for 57Gy/19f, non-inferiority could not be declared: HR 57 =1.13 (90% CI 0.98, 1.30). 10-year overall survival (95% CI) was 78.5% (75.9%, 81.0%), 82.9% (80.4%, 85.0%) and 79.9% (77.3%, 82.2%) in the 74Gy, 60Gy and 57Gy groups. Bone fractures were reported in 2% (15/700), 2% (19/771) and 3% (22/719) of patients in the 74Gy, 60Gy and 57Gy groups respectively at 10 years. The most common intervention reported was a sigmoidoscopy with 12% (79/681), 8% (60/739) and 9% (65/702) in the 74Gy, 60Gy and 57Gy groups respectively. Of those patients who underwent a sigmoidoscopy it was due to symptoms for 81% (63/78) 81% (48/59) and 85% (55/65) of patients in the 74Gy, 60Gy and 57Gy group respectively. Frequencies of all other pre-specified co-morbidities or related interventions (ureteric obstruction, bowel strictures, trans-urethral resection of prostate, urethrotomy, urethral dilatation or long term catheterisation or treatment of proctopathy with steroid, sucralfate, formalin, laser coagulation or rectal diversion) were &lt;1% in all groups. Conclusions: With a median follow-up of 12 years, oncological outcomes following 60Gy/20f continue to be non-inferior to those with 74Gy/37f. Late co-morbidities were very low across all treatment groups. These data support the long-term safety of moderate hypofractionation. Clinical trial information: 97182923 .